The Role of TFE3 in Mediating Skeletal Muscle Mitochondrial Adaptations to Exercise Training

Maintenance of a healthy mitochondrial pool is essential for skeletal muscle function. Mitophagy, the selective clearance of dysfunctional mitochondria, optimizes the mitochondrial network and heavily relies on lysosomal capacity within the tissue. The transcription factor E3 (TFE3) is a protein that activates the expression of lysosomal genes. With exercise, TFE3 is presumed to optimize the mitochondrial pool through the removal of organelles via lysosomes. However, the molecular mechanisms of the involved pathways remain unknown. Using WT and whole-body TFE3 KO mice, we sought to determine the role of TFE3 in regulating basal skeletal muscle mitochondrial function in response to acute and chronic endurance exercise. Our results suggest that the loss of TFE3 compromises beneficial training adaptations leading to improved muscle endurance and mitochondrial function and may induce a greater sensitivity to mitophagy induction in untrained muscle.